This invention relates to medical devices, such as polyvinylchloride (PVC) tubing and oxygenators that use hollow fiber membranes to replace carbon dioxide in the blood with oxygen.
Microporous hollow fiber membrane oxygenators are commonly used to support patients during heart bypass procedures such as cardiac artery bypass grafting (CABG), heart valve repair and replacement, and the like. Such oxygenators are designed to direct blood flow over (or through) the microporous hollow fibers while oxygen-rich gas flows through (or over) the fiber lumens. This results in simultaneous mass transfer of molecular oxygen and carbon dioxide in opposite directions across the membrane.
The efficiency of the device can be described by the gas transfer per unit area of membrane at a given blood flow rate, gas flow rate, and composition (i.e., the specific gas transfer rate, typically cc of gas per liters of blood flow per minute per square meter of gas transfer area).
The micropores in the microporous hollow fibers are small enough to prevent whole-blood components such as platelets and red cells from passing through to the gas side of the membrane. However, the materials used to manufacture the fiber (polypropylenes, polyethylenes) are not primarily designed for blood compatibility. Both platelets and leukocytes adhere in great numbers to the materials, leading to significant activation of deleterious responses in the blood.
Several coating methods have been used to improve blood compatibility by providing an additional layer or xe2x80x9csecond skinxe2x80x9d for the underlying structural material comprising the fiber membrane. The added layer of material provides a blood-surface interaction superior to that seen for the bulk fiber materials. For example, heparin is known to have good blood compatibility properties and has been used as a coating on several commercialized products. Unfortunately, heparin-based coatings are inherently expensive and complex due to the use of sodium heparin, a complex, costly and fragile biologically derived substance.
The Carmeda Bioactive Surface (Medtronic, Inc.) uses a polymer primer coat followed by covalent attachment of heparin to primary amino groups present in the primer coat. The Duraflo Bonded Heparin Surface (Baxter, Inc.) uses a heparin-polymer blend-based coating that is intended to achieve similar results. Other heparin-based coatings intended to improve blood compatibility are available from other medical device manufacturers (Terumo, Jostra, 3M Sarns, etc.).
Silicone (polydimethyl siloxane-based resins) is known to be compatible with blood. A process commercialized by Cobe Laboratories, Inc. uses a block copolymer polymer additive/coating that is intended to decrease platelet and leukocyte adhesion/activation.
Another problem is that, over time, the fluid component of blood (plasma) can migrate through the pores, a problem known as plasma migration or plasma breakthrough. In the case of a design in which the blood flows over the fibers and the oxygen-rich gas flows within the fiber lumens, this migration will eventually render the device inoperable by filing the lumens with liquid that impedes gas flow.
Reducing the average pore size can increase the time to failure somewhat. This is the approach taken in a fiber commercially available from Hoescht-Celanese and known under the tradename of Plasma Resistant Fiber or PRF. Further improvement is desireable.
One approach to the problem has been to use nonporous silicone membrane oxygenation systems. While no plasma can migrate through the membrane, gas transfer is very poor compared to that of microporous hollow fiber membrane oxygenators due to gas diffusion limitations through the solid polymer material.
Another approach to improving plasma breakthrough performance is to modify the microporous hollow fiber membrane. Previous coating methods have attempted to close off the pores with a thin film of silicon resin, mechanically preventing fluid migration. Specific gas transfer rates are improved compared to silicon membrane oxygenators, but are still well below the rates found in uncoated microporous hollow fiber membrane devices.
Another approach is the use of chemical vapor deposition (CVD) to deposit various coatings such as silicone resins on devices (e.g., Thoratec, InnerDyne). This approach suffers from poor specific gas transfer and also uses costly, toxic reagents. In addition, the CVD method is difficult to apply to the internal surfaces of finished products.
Biocompatibles, Inc. has a process for applying a phosphatidyl choline-methacrylate/butyl methacrylate copolymer that is intended to improve blood compatibility. BioInteractions, Inc. has a hydrogel/heparin mixture that is also intended to improve blood compatibility of blood oxygenators.
The invention is a method of coating a medical device, and the coated medical device itself. The device may be polyvinylchloride (PVC) tubing, any device comprising microporous hollow fiber membranes (such as blood oxygenators), or any other medical device which is prone to the plasma migration or plasma breakthrough problem.
The coating compound of the invention comprises alkoxysilane/alkylsilane copolymers, preferably aminoalkylsiloxane, and most preferably the aminoalkylsiloxane sold under the trade designation of MDX4-4159, commercially available from Dow Corning (see, for example, the URL at www.factor2.com/a-4159.htm).
One of the key aspects of this process is that it uses a siloxane material that cures in-place under very mild conditions. This is due to the use of an alkoxysilane/alkylsilane copolymer as mentioned above. The material cures via crosslinking of the alkoxysilane groups with each other, which occurs at room temperature in the presence of a trace of water as catalyst.
The method of coating the medical device creates a thin film of silicone on the device (including the microporous fibers of the device), but does not cover or fill the micropores with the thin film. The improved resistance to plasma breakthrough (i.e., increased time to device failure) is achieved instead by changing the surface of the fiber polymer near the pore opening to better resist the intrusion of plasma. The prepolymer is applied as a thin film via solvent; after the solvent carrier evaporates away, the prepolymer cures to a soft resin layer completely covering the treated surface. All blood contact occurs with the silicon resin rather than with the underlying material.
The result is a device with significantly greater time to failure for plasma breakthrough with specific gas transfer rates almost unchanged compared to identical uncoated devices. The process is also economically attractive, easier to implement, avoids toxic reagents, and can be used with a wider variety of finished products.